There are two projects within this research portfolio. The first is a longitudinal study of children in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) and the second is a clinical trial of riluzole - a glutamate antagonist with some preliminary evidence of benefit for adults with depression or obsessive-compulsive disorder (OCD). To date, an open-label trial has been completed in six children, with improvements observed in 5 of the 6 subjects. A double-blind, placebo-controlled trial of riluzole is underway for children ages 7 - 17 years. Enrollment is ongoing and interested individuals are invited to learn more about the study at: http://clinicalstudies.info.nih.gov/detail/A_2005-M-0225.html [unreadable] [unreadable] Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders appear to arise, in some cases, as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms begin or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The subgroup shares several common clinical characteristics and may share a common pathophysiology for their symptoms. Investigations of the nature and treatment of this novel subgroup are ongoing. During this reporting period, additional experience has been gained in determining the relationship between streptococcal infections and symptom onset, as well as the influence of GABHS infections on clinical course for children in the PANDAS subgroup and others with OCD. Children with recent-onset OCD are followed prospectively for up to two years to determine whether or not acute, dramatic onset of symptoms will predict an episodic course. Further, associations between symptom exacerbation and streptococcal infections are being tracked to determine whether or not membership in the PANDAS subgroup can be predicted at initial presentation.[unreadable] An ongoing collaboration with Drs. Madeleine Cunningham (Univ. Oklahoma) and Christina Kirvan (UC-Davis) is examining the relationship between cross-reactive antineuronal antibodies and symptoms in the PANDAS subgroup. Experiments performed by Drs. Kirvan and Cunningham with serum from the NIMH subjects has revealed the presence of cross-reactive antibodies in the PANDAS subgroup, but not in serum from healthy controls or children with non-PANDAS OCD or tic disorders. The collaboration is continuing in order to further characterize the antibodies and to determine their specificity. The collaboration with Dr. B.J. Casey concluded in 2008 with publication of a paper describing the results of neuropsychological testing of patients in the PANDAS subgroup and children with OCD.